Chemical and Biological Characterization of Mycobacterium tuberculosis-Specific ESAT6-Like Proteins and Their Potentials in the Prevention of Tuberculosis and Asthma

Abstract

Early Secreted Antigenic Target 6 kDa (ESAT6) is a potent immunogenic protein secreted by the bacteria causing tuberculosis, i.e., Mycobacterium tuberculosis. Another highly immunogenic culture filtrate protein whose gene is linked to ESAT6/ESXA is known as CFP10/ESXB. Because of their high immunogenicity and specificity to M. tuberculosis, these proteins have been proposed as a vaccine to prevent tuberculosis and diagnose the active/latent disease. However, the same proteins cannot be used for prevention and diagnosis because immunized but healthy people will also show a positive response and be falsely reported as diseased. Therefore, in this review article, the search was made to identify if any other ESAT6-like proteins exist in the M. tuberculosis genome. The search identified 21 additional ESAT-like proteins, i.e., ESXC to ESXW. Immunological characterization has shown that some of them (especially ESXV) were able to induce immune responses in vitro with cells obtained from tuberculosis patients and healthy donors. When the protein ESXV was tested in different recombinant forms (expressed in Escherichia coli, mycobacterial vectors, and DNA plasmids) and injected in mice, immune responses were induced to multiple epitopes of the protein. Furthermore, immunization of mice with ESXV protected them from infection with M. tuberculosis. The same protein was also able to protect mice against the induction of asthma. These results suggest that ESXV has the potential to protect against two major diseases of the world, i.e., tuberculosis and asthma, and hence may be used as a common vaccine for both diseases.